This central goal of this project is to further our understanding of the early events of neocortical development, it's inputs and outputs, and specifically to explore, how neurotransmitter-like molecules affect neuronal development prior to the onset of synaptogenesis. Recent evidence suggests that early in development, certain neurotransmitters, for example, glutamate, adenosine 5'-triphosphate (ATP) or serotonin, may serve functions as trophic factors or neuromodulators, regulating cell division, growth, differentiation and migration of neurons rather than mediating synaptic transmission. Although the mechanism is not fully understood, evidence is accumulating that these molecules affect these developmental processes by regulating intracellular calcium [Ca++]i. During the past year, emphasis was placed on 2 projects. In the first, I examined the differential distribution of various neurotransmitters during pre-and postnatal development of the ferret neocortex. Employing immunohistochemical methods, the development of glutamate, GABA, and glycine immunoreactivity, as well as the emergence of the ionotropic glutamate receptors, the so-called AMPA receptors GluR1 and GluR2/3 was studied. The data show that glutamate, GABA and glycine are present in the developing neocortex, and could mediate events like cellular growth and differentiation. The second project employed calcium imaging experiments on a confocal microscope setup to determine whether these early "transmitter systems" are functional. Preliminary results indicate that many of the progenitor cells in the ventricular zone (VZ) show spacially distinct patterns of spontaneous Ca++ oscillations. While most of the progenitor cells - in contrast to cells in the forming cortical plate - fail to respond to the traditional neurotransmitter agonists, ATP clearly elicits a rise in [Ca++]i in many of these progenitor cells. I am currently investigating the mechanisms of this intercellular communication between cells in the VZ.